Chemicals such as 2,3,7,8-tetrachlorodibenzo-p-dioxin and diethylstilbestrol, and naturally occurring toxins such as the tricothecene mycotoxin, T2 toxin, adversely affected immunologic function in offspring following treatment of pregnant mice over various periods of gestation. Studies are in progress to explore the relationship between developmental immunotoxicity and subsequent adult immune function. These studies are, in particular, addressing the following question: Do modulations in lymphocytic surface antigens, induced by prenatal chemical exposure, result in functional immunologic deficits later in life? TCDD, DES, or T2 toxin are administered to pregnant C57B1/6 and B6C3F1 mice during gestation to establish the sensitive period for induction of immunologic deficits and to identify the initial lesion. Fetal T and B lymphocytes from the spleen and thymus, and subpopulations of these cells, are stained immunocytochemically to determine the morphological effects of TCDD, DES, and T2 toxin on lymphocytic surface antigens and their development. Fetal thymic organ culture is used to determine effects of exposure on subpopulations of immune cells. In addition, cell populations are evaluated by flow cytometry to determine quantitative changes. If changes in these surface markers persist beyond the age of four weeks in the prenatally exposed animal, functional tests, including mixed lymphocyte reaction, plaque assay, in vitro blastogenesis, cytotoxic T lymphocyte function, and colony forming unit assay, are conducted. TCDD was found to significantly decrease fetal thymic weight and cellularity, and to significantly alter normal patterns of intrathymic differentiation as defined by thymocyte expression of the cell surface antigens CD4, CD8, J11D, PNA, and TCR. Mice exposed to TCDD were found to have significantly depressed cytotoxic T lymphocyte activity at eight weeks postnatally. DES and T2 toxin have been found to produce fetal alterations similar to, but less severe than, that seen after TCDD.